Process for the preparation of benzoyl ureas

ABSTRACT

Benzoyl ureas of the formula ##STR1## are prepared by starting from benzoyl derivatives of the formula 
     
         Q-COHal 
    
     which are converted via the corresponding azides into the isocyanates, which are in turn reacted with corresponding benzamides.

This invention relates to a novel process for the preparation of benzoylureas, which are useful as pesticides.

THE PRIOR ART

It is known to prepare benzoyl ureas by reacting a corresponding benzoicacid amide with a substituted phenylisocyanate. The isocyanate startingcompound may be prepared from a corresponding aniline by reaction withphosgene. The aniline itself may be obtained from the correspondingnitro compound by reduction.

DESCRIPTION OF THE INVENTION

We have discovered that there is a new reaction sequence which providesa technically simple method of preparing benzoyl ureas of the formula##STR2## wherein X is hydrogen, fluorine or chlorine;

Y is fluorine, chlorine, CH₃ or CF₃ ; and

Q is ##STR3## where R₁, R₂ and R₄ are each independently fluorine,chlorine, bromine, CF₃, OCF₃ or hydrogen;

R₃ is fluorine, chlorine, bromine, CF₃, OCF₃, hydrogen, ethoxysubstituted by four to five fluorine and/or chlorine atoms, phenyl whichis mono- or polysubstituted by fluorine, chlorine, bromine, CH₃, CF₃,OCF₃, OCF₂ CHF₂ OC₂ F₅, NO₂ or CN; or pyridyloxy which is mono- orpolysubstituted by fluorine, chlorine or CF₃ ; or R₂ and R₃ or R₃ andR₄, together with each other, are --O--CF₂ --CF₂ --O--.

X and Y are preferably the pairs F/H, F/F, Cl/H, Cl/Cl or Cl/F. Examplesof Q are:

-4-Chlorophenyl,

-2,3,4,5-tetrafluorophenyl,

-2,3,4,5-tetrachlorophenyl,

-3,5-dichloro-2,4-difluorophenyl,

-3,5-dichloro-4-pentafluoroethoxyphenyl,

-3,5-Dichloro-4-[1,1,2,2-tetrafluoroethoxy]phenyl,

-3,5-Dichloro-4-trifluoromethoxyphenyl,

-3,5-Dichloro-4-[(3-chloro-5-trifluoromethyl-pyridin-2-yl)oxy]phenyl,

-3-Chloro-4-[(3-chloro-4-trifluoromethyl)phenoxy]phenyl,

-3-(4-Trifluoromethylphenoxy)-phenyl,

-3-(3-Trifluoromethylphenoxy)-phenyl,

-3-(2-Trifluoromethylphenoxy)-phenyl,

-3,4-(Tetrafluoroethylenedioxy)-phenyl,

-4-Trifluoromethylphenyl and

-4-Trifluoromethoxyphenyl.

The various substituents may be identical or different within the scopeof the above definition. Alkyl groups may be straight-chained orbranched. In the case of polysubstitution, CN, CF₃, OCF₃, OC₂ F₅, OCF₂--CF₂ H occur only once, whereas halogen atoms, either identical ordifferent, may occur up to six times.

The process according to the invention proceeds through the followingstages: ##STR4##

In formula (II) Z is a substituent which may be replaced by the azideion.

Examples includes: fluorine, chlorine, bromine, iodine and groups of theformula O--R₆ wherein R₆ is lower alkyl, phenyl, benzyl, loweralkoxycarbonyl, phenoxycarbonyl, lower alkylcarbonyl or benzoyl.

The halogens fluorine and chlorine are preferred.

Lower alkyl radicals are methyl, ethyl, propyl, isopropyl, n-butyl,isobutyl, sec.butyl and tert.butyl.

Examples of azides include sodium azide, potassium azide and calciumazide.

The steps may be carried out one after the other in the same reactionmedium without isolation of the intermediate products. Steps 1 and 2 arecarried out at temperatures between about 80° C. and the boiling pointof the reaction mixture, taking care to avoid temperatures above 180° C.The range between about 100° and 140° C. is preferred. The reactionconstitutes thermal degradation of a carboxylic acid via the carboxylicacid azide to yield the isocyanate by Curtius degradation. Decompositionof the azide is effected so that no substantial quantities thereofremain in the reaction mixture. Suitable solvents include, inparticular, halogenated benzenes, such as chlorobenzene, dichlorobenzeneand high-boiling-point ethers, and also aromatic hydrocarbons such astoluene.

Further reaction of the isocyanate with the amide V is carried out byadding the amide V to the solution of the isocyanate and stirring themixture at temperatures between about 80° and 160° C., preferablybetween 90° and 130° C. Depending on the reactivity of the componentsand the reaction temperature, the reaction time is up to several hours.

The method of synthesis according to the present invention via thecompounds III, which have heretofore not been described, makes itpossible to avoid the highly undesirable reaction with phosgene (VIII).

The compounds of the formula I are obtained with good yields and highpurity without isolation of the intermediate in the individual steps.

Examples of the compounds which may advantageously be prepared accordingto the invention are the compounds disclosed in GermanOffenlegungsschriften 23 23 236, 25 04 982, 25 97 944, 25 31 279, 25 37413, 26 01 780, 27 26 684, 30 03 112, 30 26 825, 30 41 947, 32 23 505,32 32 265 and 32 35 419 and in published European applications 52 833and 57 888.

The following compounds should be mentioned in particular:

N-(2,4-Difluoro-3,5-dichlorophenyl)-N'-(2,6-difluorobenzoyl)-urea,

N-(3,5-Dichloro-4-pentafluoroethoxyphenyl)-N'-(2,6-difluorobenzoyl)-urea,

N-[3,5-Dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl)-N'-(2,6-difluorobenzoyl)-urea,

N-(2,3,4,5-Tetrafluorophenyl)-N'-(2,6-difluoro-benzoyl)-urea,

N-(2,3,4-Trifluoro-5-chlorophenyl)-N'-(2,6-difluorobenzoyl)-urea,

N-(2,3,4,5-Tetrachlorophenyl)-N'-(2,6-difluoro-benzoyl)-urea,

N-[3,5-Dichloro-4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-phenyl]-N'-(2,6-difluorobenzoyl)-urea,

N-(4-Methoxyphenyl)-N'-(2-chlorobenzoyl)-urea, and

N-(4-Trifluoromethylphenyl)-N'-(2,6-difluoro-benzoyl)-urea.

With regard to the correlation between structure and activity in benzoylureas with an insecticidal effect, it is known that compounds which aremono- or disubstituted in the ortho-position in the benzoyl moiety offormula I and compounds which are mono- or disubstituted in themeta-position in the aniline moiety of formula I are particularlyeffective. In the aniline moiety the ortho- and/or para-position may befree or substituted.

Conventional methods of synthesizing benzoyl ureas of the formula Icomprise the folling reaction sequences: ##STR5##

In method A as well as in method B of the conventional syntheses, theaniline moiety is introduced into the synthesis either directly in theform of an aniline (VII) or in a preceding phosgenation step B₁ in theform of the isocyanate (IV).

On the one hand, the amino group of the aniline (VII) as a substituentin electrophilic aromatic substitution reactions directs the newlyintroduced electrophile preferably into the ortho or para position. Onthe other hand, however, compounds of the formula (I) show particularlygood insecticidal activity when they carry one or more, preferablyhalogen substituents in the meta-position of the aniline moiety. Thismeans, that, in order to prepare the aniline (VII), it is not possibleto start from the aniline (VII, R₁ -R₄ =H) or from suitable anilinessubstituted by R₁ and R₄ (VII, R₃, R₅ .H), but rather that analternative route must be found via a nitrobenzene (IX) ##STR6## inwhich the substituents R₂ and/or R₄ are introduced by making use of themeta-directing effect of the nitro group. The nitro compound (IX) isthen reduced to form the aniline (VII).

By contrast, the process according to the present invention starts froma benzoic acid derivative of the formula (II) in which the carboxylicacid function in (II) as a meta-directing substituent may alsoadvantageously be used to build up the substitution pattern R₁ to R₄ bymeans of nucleophilic and electrophilic substitution reactions in thebenzene ring:

in order to introduce halogen substituents: possibly starting frombenzoyl chloride by stepwise chlorination to form the mono-, di-, tri-or tetrachlorobenzoylchloride.

In order to create the 2,4-dichloro-3,5-dichlorophenyl substitutionknown from German Offenlegungsschrift 30 44 055 from2,3,4,5-tetrachlorobenzoyl chloride with fluoride ions to form the2,4-difluoro-3,5-dichlorobenzoylfluoride, possibly analogously topublished European application 164 619.

In halogen exchange reactions, such as chlorine-fluorine exchange, ifbenzoylchlorides are used as starting materials, apart from the halogenexchange in the nucleus of the aromatic ring the halogen of the acidhalide function is also exchanged, and the resulting benzoyl fluoride(II) (Z=F) reacts with azides in reaction step 1 more rapidly andtotally than the corresponding acid chloride (II) (Z=Cl).

The following examples illustrate the present invention and will enableothers skilled in the art to understand it more completely. It should beunderstood, however, that the invention is not limited solely to theparticular examples given below.

EXAMPLE 1N-(2,3,4-Trifluoro-5-chlorophenyl)-N'-(2,6-difluoro-benzoyl)-urea

(a) In a three-necked flask, 0.62 g of sodium azide in 30 ml ofchlorobenzene were heated to 120° C. while stirring. At thistemperature, first one third of a solution of 1.9 g of2,3,4-trifluoro-5-chlorobenzoylfluoride in 10 ml of chlorobenzene wasadded dropwise. After a few minutes, when the evolution of nitrogen hadstarted, the remainder of the solution was added dropwise within 10minutes. During this time, the evolution of nitrogen became lively. Whenit stopped, the mixture was allowed to react for a half hour more. Aftercooling to 25° C., 0.5 g of kieselguhr were added, and the mixture wassuction-filtered. The filtrate, which was a solution of2,3,4-trifluoro-5-chlorophenylisocyanate in chlorobenzene, was used forthe next reaction step.

(b) The filtrate from (a) was mixed with 1.42 g of2,6-difluorobenzamide, which had previously been dried for 3 hours at60° C. in vacuo, and the mixture was heated at about 100° C., whilestirring, until a clear solution had formed. The solution was thenstirred for 7 hours at 100° C. It was allowed to cool to 70° C. and wasthen evaporated to dryness in vacuo. The residue was stirred with 30 mlof acetone at 40° to 50° C., cooled to 10° C., suction-filtered anddried.

Yield: 2.1 g (64% of theory), m.p. 222°-224° C., of the title compound.

(c) The precursor, 2,3,4-trifluoro-5-chlorobenzoyl fluoride (b.p. 67mbar: 97°-100° C.), was obtained in addition to2,4-difluoro-3,5-dichlorobenzoyl fluoride (b.p. 67 mbar: 127°-129° C.)when 41.7 g of 2,3,4,5-tetrachlorobenzoyl chloride were heated at 200°C. with 43.5 g of potassium fluoride in 450 ml of sulfolane for 8 hours,and the reaction mixture was distilled in vacuo.

EXAMPLE 2N-(2,4-Difluoro-3,5-dichlorophenyl)-N-(2,6-difluoro-benzoyl)-urea (a)2,4-Difluoro-3,5-dichlorobenzoyl fluoride

Analogous to Example (1b), the title compound was obtained with a yieldof more than 70% by reacting 2,3,4,5-tetrachlorobenzoyl chloride withpotassium fluoride in sulfolane. The reaction temperature was 150° C.,and the reaction time was 8 hours.

(b) Reaction of 2,4-difluoro-3,5-dichlorobenzoyl-fluoride with sodiumazide

11.45 g of 2,4-difluoro-3,5-dichlorobenzoyl fluoride was added dropwiseto a suspension of sodium azide (3.25 g) in toluene (40 ml) heated toabout 100° C., and the course of the reaction was monitored by means ofthe nitrogen gas given off. After all the acid fluoride had been addedthe mixture was stirred for another hour at 110° C., during which sodiumfluoride crystals were precipitated.

(c) Reaction of 2,4-difluoro-3,4-dichlorophenylisocyanate with2,6-difluorobenzamide

7.9 g of 2,6-Difluorobenzamide were added to the suspension obtained in(b), and the reaction mixture allowed to stand for 10 hours at about 95°C. A white crystalline slurry precipitated during that time. Aftercooling, the precipitate was separated by suction filtration. 18.45 g ofa mixture of sodium fluoride and benzoyl urea were isolated. The crudeproduct thus obtained was extracted with boiling acetone and filtered.16.2 g of N-(2,4-difluorobenzoyl)-urea were isolated from the filtrate(84.36% of theory).

EXAMPLE 3N-(2,4-Difluoro-3,5-dichlorophenyl)-N'-(2,6-difluoro-benzoyl)-urea

A solution of 23 g (0.100 mol) of 2,4-difluoro-3,5-dichlorobenzoylfluoride in 100 ml of chlorobenzene was slowly added dropwise to a hot(125° C.) mixture of 7.0 g (0.105 mol) of sodium azide and 300 ml ofchlorobenzene, while vigorously stirring. Nitrogen was given off. Forsafety reasons, the addition is regulated so that the quantity ofbenzoyl fluoride added dropwise corresponds to the rate of rearrangementof the Curtius degradation, which can be monitored by means of thenitrogen given off.

After all of the solution had been added, the mixture was allowed toreact for 30 minutes more, then 3 g of kieselguhr were added, themixture was allowed to cool to about 30° C., and the insoluble matter issuction-filtered off.

15.7 g (0.10 mol) of 2,6-difluorobenzamide were added to the filtrateand the mixture was heated at 100° C. for about 7 hours. The reactionmixture was worked up as described in Example 1.

Yield: 28.8 g (75.3% of theory), m.p. 221°-224° C., of the titlecompound.

While the present invention has been illustrated with the aid of certainspecific embodiments thereof, it will be readily apparent to othersskilled in the art that the invention is not limited to these particularembodiments, and that various changes and modifications may be madewithout departing from the spirit of the invention or the scope of theappended claims.

We claim:
 1. The method of preparing the compound of the formula ##STR7## which comprises reacting a benzoyl derivative of the formula ##STR8## in an inert solvent said benzoyl derivative and inert solvent forming a reaction mixture, at elevated temperatures of between about 80° C. and the boiling point of the reaction mixture, with an alkali metal azide or an alkaline earth metal azide to form the azide intermediate of the formula ##STR9## thermally degrading, at a temperature between about 80° C. and the boiling point of the reaction mixture, said azide intermediate in situ in the reaction mixture to form the isocyanate intermediate of the formula ##STR10## reacting said isocyanate intermediate in situ in the reaction mixture at elevated temperatures with the benzamide of the formula ##STR11## and recovering the reaction product.
 2. The method of claim 1, wherein said inert solvent is chlorobenzene. 